Genetic Link Associated With One Percent Of All Cancerous Tumors Discovered

Scientists have located a single gene that is at least partially responsible for the development of one percent of all cancerous tumors, according to new research appearing in the advanced online edition of the journal Nature Genetics.

The gene in question is CUX1, and according to the study authors, this is the first time it has been broadly associated with the onset of cancer. The researchers found that when CUX1 is deactivated, a biological pathway that increases tumor growth becomes activated. Drugs inhibiting this biological pathway are currently being developed and could offer a new treatment for patients that have this particular cancer-causing mutation.

“Our research is a prime example of how understanding the genetic code of cancers can drive the search for targeted cancer therapies that work more effectively and efficiently,” lead author Dr. David Adams of the Wellcome Trust Sanger Institute said in a statement Sunday. “This could improve the lives of thousands of people suffering from cancer.”

Dr. Adams and his colleagues used genetic information from more than 7,600 patients whose DNA was collected and sequenced by groups such as the International Cancer Genome Consortium (ICGC). They discovered that mutations deactivated CUX1 in approximately one percent of the cancer genomes they analyzed.

These types of mutations are associated with tumor growth, and while the study authors said that they occur at relatively low frequency, they have been observed across several different types of cancer. Previous research focusing on genetic mutations looked at those occurring at high frequency unique to specific types of cancer, thus missing the rarer but more widespread CUX1 as a potential cancer catalyst.

“Our work harnesses the power of combining large-scale cancer genomics with experimental genetics,” explained first author Dr. Chi Wong, also of the Wellcome Trust Sanger Institute and a hematologist at Addenbrooke’s Hospital in Cambridge. “CUX1 defects are particularly common in myeloid blood cancers, either through mutation or acquired loss of chromosome 7q. As these patients have a dismal prognosis currently, novel targeted therapies are urgently needed.”

“Data collected from large consortia such the ICGC, provides us with a new and broader way to identify genes that can underlie the development of cancers,” added Professor David Tuveson from Cold Spring Harbor Laboratory. “We can now look at cancers as groups of diseases according to their tissues of origin and collectively examine and compare their genomes.”

In order to determine who deactivating CUX1 could lead to tumor development, they inhibited it in cultured cells and found that it had a “knock-on effect” on the biological inhibitor PIK3IP1. With its effects hampered, phosphoinositide 3-kinase (PI3K) – an enzyme responsible for cell growth – becomes active and increased the rate of tumor progression, the investigators said.

“Drugs that inhibit PI3K signaling are currently undergoing clinical trial,” said Professor Paul Workman, Deputy Chief Executive and Head of Cancer Therapeutics at The Institute of Cancer Research. “This discovery will help us to target these drugs to a new group of patients who will benefit from them and could have a dramatic effect on the lives of many cancer sufferers.”